Antidepressants (ADs) are the most frequently prescribed class of psychotropic medications and the most common treatment for depression and anxiety disorders-yet patient adherence is poor and is widely viewed as contributing to reduced effectiveness. Fortunately, AD adherence can be improved via interventions consistent with the Chronic Care Model (CCM). However, traditionally- delivered adherence promotion programs are complex, staff-intensive, and costly-barriers to wider adoption, implementation, and maintenance of these programs in real-world settings. Our aim is to carry out a trial of a low-cost, IT-enabled AD adherence program, specifically a direct-to-patient, automated telephone interactive voice recognition (IVR) intervention to boost patient AD persistence. This intervention is consistent with the CCM but is much more amenable to widespread dissemination over a large population. In an initial startup period we will adapt and pilot existing IVR adherence calls and scripts, informed by formative focus groups and interviews with key informants (patients, providers). Following this, we will conduct a pragmatic, randomized clinical trial enrolling 3,100 HMO members ages 21 to 75, recently started on an incident course of AD medications for associated unipolar depression and/or anxiety diagnoses. Participants will be randomized 1:1 to either a treatment as usual (TAU) control condition or to TAU plus the IVR automated telephone program. Recruitment will continue for 18 months, with periodic participant-level follow-up for 40 weeks. The IVR program will deliver reminder and/or tardy calls timed to projected AD refill dates. The intervention also optionally offers brief psycho-education, or transfer to a live pharmacist or the HMO mail refill pharmacy. The primary outcome will be the Estimated Level of Persistence with Therapy (ELPT) for ADs, based on prescription refill data abstracted from the HMO's electronic medical record (EMR). We hypothesize that participants in the IVR study arm will have a significantly higher rate of AD persistence than those in the TAU control condition. Secondary medication adherence outcomes include continuous measure of medication acquisition (CMA) and continuous measure of medication gaps (CMG). Other secondary outcomes include self-report depression and anxiety symptoms, general health status, patient and provider satisfaction, and healthcare costs and usage. We will also conduct cost-effectiveness analyses (CEA) to assess the value-for-money (cost per depression free day gained, and cost per quality adjusted life year gained) of the IVR technology compared to TAU. Costs will include IVR development and implementation as well as EMR-derived healthcare utilization data (visits, medications, etc.), augmented with participant report of out-of-plan services. Finally, evaluative qualitative interviews will be conducted with key stakeholders to identify barriers/facilitators of intervention implementation-keys for future dissemination. PUBLIC HEALTH RELEVANCE: Persons taking antidepressant medication often stop too early to get full benefit. Programs exist to help these patients stay on medication longer, but most are too complicated and costly to be widely used. This study will test an automated telephone calling program to help patients obtain refills at the right time and stay on antidepressants longer. This program is low cost and can be delivered to widespread populations much more easily than other approaches.